12-acylaminosteroid of the pregnane series



United States Patent 3,188,303 12-ACYLAMINOSTEROHD 0F TIE PREGNANE SERESKanzo Sasaki, Osaka-shit, and Junichi Kawanami, Toyo naka-shi, Japan,assignors to Shionogi & (30., Ltd,

Osaka, Japan No Drawing. Filed Apr. 16, 1963, Ser. No. 273,320 Claimspriority, appli jcaiinggapan, Apr. 20, 1962,

19 Claims. (Cl: 260-239.55)

The present invention relates to l2-acylaminosteroids and productionthereof. More particularly, it relates to IZ-acylaminosteroids ofpregnane series possessing antiprogestational activity and productionthereof.

The said l2-acylaminosteroid of pregnane series is representable by thefollowing formula:

s5 CU wherein R represents a hydrogen atom or a lower alkyl group (e.g.methyl, ethyl, propyl), X and Y each represents a methylene group, ahydroxymethylene group, a formyloxymethylene group, a loweralkanoyloxymethylene group (e.g. acetyloxymethylene,propionyloxymethylene, butyryloxymethylene), a carbonyl group, a loweralkylenedioxymethylene group (e.g. ethylenedioxymethylene,trimethylenedioxymethylene) or a di(lower) alkoxymethylene group (e.g.dimethoxymethylene, diethoxy- CH3 N z l wherein X and Y each has thesame significance as designated above, a double bond can exist betweenthe S-position and the adjacent position thereto and, when it does notexist, the hydrogen atom at the 5-position has OL- or {3- configuration,and the ripple mark (3) is a generic indication of both aandfl-configurations, to acylation.

The starting IZ-aminosteroid of Formula II may be prepared, forinstance, by subjecting the corresponding 12-oxosteroid of pregnaneseries to oximation (oxime formation) and subjecting the resultant12-hydroxyiminosteroid of pregnane series to reduction. The concreteprocedure for preparation of the 12-aminosteroid (II) has been describedin detail in copending application Ser.

3,1883% Fatented June 81, 1965 Ice No. 196,472 of H. Mitsuhashi, filedMay 21, 1962 (now US. Patent No. 3,113,130).

The acylation is accomplished by treating the, 12-aminosteroid (II) witha conventional acylating agent represented by the formula:

wherein R has the same significance as designated above, and Rrepresents a hydroxyl group, a lower alkoxy group (e.g. methoxy, ethoxy,propoxy), a halogen atom or a group represented by the formula: -..-OCORwherein R has the same significance as designated above, under thereaction conditions which are usually adopted on the use of the saidacylating agent. For instance, the object is attained by treating theIZ-aminosteroid (II). with a carboxylic anhydride of Formula III whereinR is a group represented by the formula: -OCO-R at a temperature fromroom temperature (15 to 30 C.) to reflux temperature, if necessary, inan inert organic solvent (e.g. benzene, toluene, dichloromethane,chloroform, pyridine, picoline).

The said process results in the acylation of the amino group at thel2-position. The hydroxyl group(s), if any, at the 3 and/or 20position(s) may be simultaneously acylated depending on the reactionconditions. Generally speaking, higher reaction temperature such asreflux tends to cause the simultaneous acylation of the said hydroxyl p(The thus-produced 12-acyl'aminosteroid (I) possesses anti-progestationalactivity. In the test using rabbits, for instance,3,20-dioxo-IZa-acetylamino-4-pregnene produced significant inhibition ofprogestational response caused by the subcutaneous treatment of 4milligrams of progesterone, when administered at a dose of 2.5milligrams per horn by intrauterine injection. Other12-acylaminosteroids of Formula I also possess the similar activity.Accordingly, they are useful as anti-progestational agents. In addition,it may be noted that they show anesthetic activity. For instance, when3,20-dioxo=12,6-acetylamino- '5,Bpregnane was subcutaneouslyadministered to mice at a dose of 50 milligrams and 250 milligrams perkilogram of body weight, the anesthetic state was maintained for 1.5hours and more than 3 hours, respectively.

Practical and presently-preferred embodiments of the present inventionare illustratively shown in the following examples. In these examples,the abbreviations have the following significances: mg., milligram(s);g., gram(s), ml., millilitre(s); Anal. Calcd., analysis calculated; and(3., degrees centigrade. Other abbreviations have conventionalsignificances.

EXAMPLE 1 Preparation of 3,3,20,20 bisethylenedioxy 12a acetylaminp 5(6) pregnene and 3,3,20,20 bisethylenedioxy-I ZB-acetylamino-j (6)-pregnene on, on,

| 0 v 0 NH; (3 1 OHaCO-NH 1 A mixture (642 mg.) of3,3,20,20-bisethylenedioxy-12aamino-5(6)-pregnene and3,3,20,20-bisethylenedioxy-12B- amino-(6)-pregnene is dissolved in amixture of pyridine (6 ml.) and acetic anhydride (6 ml.), and theresultant mixture is allowed to stand at room temperature (15 to 30 C.)One overnight. To the reaction mixture, there is added water whilecooling with ice. The resulting mixture is shaken with ether. The etherextract is washed with water, aqueous sodium carbonate and Water inorder. During the washing procedure, there are separated crystalsbetween the aqueous phase and the organic solvent phase, the crystalsbeing collected by filtration and recrystallized from methanol to give3,3,20,20-hisethylenedioxy-12a-acetylamino-5(6)-pregnene (100 mg.) asneedles melting at 202 to 205 C. The organic solvent phase is dried andevaporated. The resultant oil is crystallized from methanol to give3,3,20,20-bisethylenedioxy-12(3- acetylamino-S(6)-pregnene (109 mg.) asneedles melting at 138 to 141 C.

3,3,20,20 biseflzylenedioxy 12a acetylamino 5(6)- pregnene.- [a] 88 :2(chloroform).

IR: vflllif 3422, 1662, 1501, 1377, 1097, 1052, 1034,

Anal. Calcd. for C H O NCH GH: C, 68.40; H, 9.23; N, 2.85. Found: C,68.26; H, 9.18; N, 3.27.

3,3,20,20 bisethylenedz'oxy 12B acetylamiizo 5 (6 pregene.--[u] -32:2(chloroform).

IR: vf,,,,;f 3627, 3341, 1651, 1533, 1378, 1117, 1093,

Anal. Calcd. for C H4 O NJ/zCH OH: C, 69.42; H, 9.11; N, 2.95. Found: C,69.57; H, 9.20; N, 3.00.

The starting material of this example, a mixture of 3,3,20,20-bisethylenedioxy 12a amino 5(6) pregnene and 3,3,20,20bisethylenedioxy-l2}8-amin0-5(6)-pregnene, is prepared from3,20-dioxo-l2a-acetyloxy-4-pregnene [Just et al.: J. Org. Chem, vol. 23,page 12 (1958)] according to the following scheme:

Ketalatlon Heating with ethylencglycol and sultonic acid around 80 C.

Deacctylation Rcfluxing with potassium hydroxide in pyridine and aqueousethanol.

Oxidation Stirring with chromicacid and pyridine at room temperature.

n two Q3 [ZQQ Oximation Refluxing with hydroxylarnjne in ethanol,

Reduction Refluxing with metallic sodium and propanol.

EXAMPLE 2 Preparation of 3,20-di0x0-12ot-acetylamirzo-4-pregnene and3,20-di0x0-125-acetylamino-4-pregnene CH3CO-NH 1 Anal. Calcd. for C H ON: C, 74.36; H, 8.95; N, 3.77. Found: C, 74.14; H, 8.99; N, 3.50.

The starting material of this example, a mixture of 3,20dioxo-l2a-amino-4-pregnene and 3,20-dioxo-12B-amino- 4-pregnene, isprepared from a mixture of 3,3,20,20-bis- 5 ethylenediOXy-IZa-aminO-S(6)-pregnene and 3,3,20,20- bisethylenedioxy-12/3-amino-5 (6)-pregnene[cf. Example 1 of this specification] according to the following scheme:

Preparation of 3,3,20,20 bisethylenedioxy 12a acetylamino 5/3 pregneneand 3,3,20,20 bisethylenedioxy- CHaCO-NH (L 1 a5 [3Q 713C,

A mixture (2.5 g.) of 3,3,20,20-bisethylenedioxy-12aamino-SB-pregnaneand 3,3,20,20-bisethylenedioxy-12,8- amino-SB-pregnane is dissolved in amixture of pyridine ml.) and acetic anhydride (25 ml.), and theresultant solution is stirred for 2 hours at 90 C. Aften concentrationof the reaction mixture under reduced pressure to a half volume, thecondensate is combined with Water. The precipitatedcrystals arecollected by filtration, washed with Water and recrystallized frommethanol to give 3,3, 20,20-bisethylenedioxy 120a acetylamino 5Bpregnane (962 mg.) as crystals melting at 219 to 222 C. The motherliquor from which the crystals were separated above is shaken withether. The ether extract is washed with water, dried and the solventevaporated. The resulting oil is treated with methanol to give3,3,20,20-bisethylenedioxy-12,8-acetylamino-SB-pregnane (1.33 g.) ascrystals melting at 132 to 135 C.

3,3,20,20 bisethylenedioxy 12a acetylamino 5ppregnane.[a] +99;L-2(chloroform).

IR: vfliif 3451, 1667, 1502, 1097, 1057, 1032, 1000,

947 cmr Anal. Calcd. for C H O N: C, 70.25; H, 9.39; N, 3.03. Found: C,70.15; H, 9.47; N, 3.28.

3,3,20,20. bisethylenedz'oxy 12,6 acetylamino 5,3- pregnane.[a] +41:2(chloroform). IR: u' 3350, 1660, 1525, 1118, 1096, 1038, 1015,

1000, 946, 876 cm.- Anal. Oalcd. for C H O NJ/2CH OH: C, 69.13; H, 9.50;N, 2.93. Found: C, 69.32; H, 9.50; N, 3.23.

The starting material of this example, a mixture of 3,3,20,20hisethylenedioxy amino 5B pregnane and 3,3,20,20 bisethylenedioxy 12Bamino 5 3 pregnane, is prepared from3,3,20,20=bisethylened-ioxy-12a-hydroxy-SB-pregnane [Engel et al.: J.Org. Chem, vol. 26, page 2869 (1961)] according to the following scheme:

HQ I

Oxidation O Stirring with chromic acid and pyridine 0 at roomtemperature Oximation Heating with hydroxylamine in ethanol and pyridineon a steam bath Reduction Preparation of3,20-di0x0-12a-acetylamino-Sfi-pregnane and3,20-di0x0-1Zfi-acetylamin0-5/3-pfegnane CH5: CH3 15H: (l)=0 CHaCO-ETH{1:0

A mixture of 3,20-dioxo-12a-amino-5B-pregnane and3,20-dioXo-1Zfl-amino-Sfl-pregnane is subjected to acetylat-ion as inExample 3 whereby 3,20-dioxo-12a-acetylarninofi-pregnane and 3,20-dioxo1Zfl-acetylamino SB-Preg: nane are obtained as prisms melting at to 162C. (crystallized from methanol) and blocks melting at 154 to 155 C.(crystallized from ether), respectively.

3,20 dioxo 12oz acetylamino 5p-pregrzane.[a] +1562? (chloroform).

Anal. Calcd. for C H O NCH OH: C, 71.07; H, 9.69; N, 3.45. Found: C,70.89; H, 9.78; N, 3.76.

3,20dix0-1ZB-acetylamin0-5fi-pregnane.[11 +25 :2" (chloroform).

IR: Val 3431,3366,1705, 1662, 1511, 1162,1008 cmr Anal. Calcd. for C H ON: C, 73.95; H, 9.45; N, 3.75. Found: C, 73.93; H, 9.54; N, 3.87.

The starting material of this example, a mixture of 3,20 dioxo12a-amino-5B-pregnane and 3,20-dioxo-12flamino-Sfi-pregnane, is preparedfrom a mixture of 3,3,20, 20-bisethy1enedioxy-IZa-aminQ-SQ- regnane and3,3,20,

'ZO-bisethylenedioxy-IZfl-arrnnO-SB- regnane (cf. Example 3 of thisspecification) according to the following scheme:

0 NH: 1 E

O Deketalation Refluxing with hydrochloric 0 acid in acetone Example 5Preparation of 35,20p-dihydr0xy-12fl-formylamino-5apregnane and3fl-f0rmyloxy-IZfi-formylamins-20,841 droxy-Sa-pregnane a NHs CH(OH) Asolution of 35,205-dihydroxy-IZB-arnino-Sa-pregnane (1.0 g.) in ethylformate (35 ml.) is heated for hours at 100 C. in an autoclave. Thereaction mixture is filtered to separate the crystallized pillars (620mg). The filtrate is condensed and treated with a mixture of methanoland acetone. The precipitated crystals (102 mg.) are collected byfiltration, combined with the above separated pillars and recrystallizedfrom a mixture of methanol and acetone to give3,8,205-dihydroxy-12,13-f0rmylamino- .5 a-pregnane (630 mg.) as crystalsmelting at 246 to 248 C. The mother liquor from which the crystals wereseparated above is evaporated and the residue (300 mg.) chromatographedon alumina. The eluate with benzenechloroform (5:1) is evaporated andcrystallized from acetone to giveSfl-formyloxy-l2fl-formylamino-20/3-hydroxy-5a-pregnane (70 mg.) ascrystals melting at 188 to 189 C.

3 8,205 dihydroxy 12,8 formylamiim-Sa-pregrmne. [M -25i2 (methanol).

IR: 11:22? 1668, 1560 cm.

Anal. Calcd. for C22H3703N: C, 72.68; H, 10.26; N, 3.85. Found: C,72.68; H, 10.39; N, 3.71.

3 3 formyloxy 12-formylamin0-205-hydroxy-Sa-pregnane.-[a] 20:2(methanol).

IR: 1 22i? 1730, 1670, 1535, 1182 cm.

Anal. Calcd. for C H O N: C, 70.55; H, 9:53; N, 3.58. Found: C, 70.74;H, 9.68; N, 3.66.

The starting material of this example, 3,3,205-dihydroxy- 12B amino 50cpregnane, is prepared from 3520,3411- hydroxy-l2-oxo-5a-pregnane [Kirket al.: J. Chem. Soc., page 1046 (1957)] according to the followingscheme:

CH3 3 (OK lH (OH) p Oxiznation Refluxing with E0 1 h dro lamina 11? ethl aol.

HOIfiT H (OH) Reduction Rcfluxing with HO metallic sodium H and propanolC H3 x ('JHKOH) H Example 6 Preparation of 3 ,8,20,6-dihydr0xy-1 2ocfol'mylam i n0-5 ozpregnane CH3 CH3 1 in, +H(OH) no o-ayn (:JH(OH) HO-a I a A solution of 3,3,20p-dihydroxy-12u-amino-5a-pregnane (380 mg.) inethyi formate (30 ml.) is heated for 15 hours at 100 C. in an autoclave.After concentration of the reaction mixture under reduced pressure, theresidue is crystallized from ethyl acetate to give 3,6,20,8-dihydroxy-1Za-fOrmyIaminQ-Su-pregnane (320 mg.) as crystals melting at 264 to 266C. [M +53i2 (methanol).

IR: v23? 1660, 1640, 1550 cm.

Anal. Calcd. for C H O N: C, 72.68; H, 10.26; N, 3.83. Found: C, 72.35;H, 10.42; N, 3.84.

The starting material of this example,35,2013-dihydroxy-l2a-amino-5u-pregnane, is prepared from 3,8,20,8-

15 dihydroxy-lZ-hydroxyimino-5 x pregnane (cf. Example 5 of thisspecification) according to the following scheme:

a HON CH(OH) Reduction HO aluminum hydride in tetrahydroluran CH3 n11,omen EXAMPLE 7 Preparation of 3B,2Jo-dillydroxy-lZ/B-acetylamino-Sapregmme (3H3 CH3 N112 (IJH(OH)CH3CO-1TIH {311(01'1) H on A solution of 35,205-dihydroxy-12fl-amino 51xpregnane (l g.) in chloroform (20 ml.) is combined with acetic anhydride(5 ml.) and the resultant mixture is stirred for 30 minutes at roomtemperature to 30 C.) The precipitated crystals are collected byfiltration, combined With n-heptane and evaporated under reducedpressure to dryness. The resulting dried crystals are recrystallizedfrom a mixture of methanol and chloroform to give 3,6,20fi-dihydroxy 12Bacetylamino 51x pregnane (992 mg.) as crystals melting at 294- to 296 C.[a] -35.9i2 (chloroform-methano1=1:1).

Anal. Calcd. for C H O N: C, 73.16; H, 10.41; N, 3.71. Found: C, 73.18;H, 10.72; N, 3.79.

H H A solution of 3 5,20B-dihydroxy-l2a-amino 5oz pregnane (1.0 g.) inchloroform (20 ml.) is combined with acetic anhydride (5 ml.), and theresultant mixture is stirred for 30 minutes at room temperature (15 to30 C.). After removal of chloroform under reduced pressure, the residueis combined with Water mL), madev to alkalinity With aqueous potassiumcarbonate and shaken With chloroform. The chloroform extract is washedwith Water, dried over anhydrous sodium sulfate and the solvent removed.The residue is combined with n-heptane and evaporated under reducedpressure to dryness. The dried substance is crystallized from ethylacetate to give 3/3,20,B-dihydroxy-12u acetylamino 5a pregnane) (738mg.) as crystals melting at 250 to 252 C. [011 +25 12(chloroform-methanol: 1 l

IR: 1315 3300, 1625, 1552 omf Anal. Calcd. for C23H3903N: c, 73.16; H,-10.41; N,

A mixture of 35,20,8-dihydroxy-12/i amino 5a pregnance (500 mg.) andacetic anhydride (10 ml.) is heated for 1 hour while refluxing. Afterremoval of acetic anhydride under reduced pressure, the residue iscombined with Water and shaken With ether. The ether extract ischromatographed on alumina for purification whereby there is obtained35,2013-diacetyloxy-12B-acetylamino-5apregnane (153 mg.) as crystalsmelting at 211 to 212.5 C. +12i4 (chloroform).

IR: V5531? 3898, 1721, 1674, 1514, 1269 cmr Anal. Calcd. for C H O N: C,70.25; H, 9.39; N, 3.03.

Found: C, 70.03; H, 9.47; N, 3.09.

EXAMPLE 10 Preparation of 3/3,20B-diacetyl0xy-12u-acetylamino-SapregmmeCH3 JJEKOH) NHZ IR: 1123?," 3317, 1735, 1636, 1539, 1252 (Em-" Anal.Calcd. for C27H43O5N C, 70.25; H, 9.39; N, 3.03. Found: C, 70.08; H,9.38; N, 3.02.

EXAMPLE 11 Preparation of 3,6-hydrxy-12,B-acetylaminn-20,8acetyloxy-Sa-pregnane CH CHzCO-NH CIKOCOCHa) OH CO-NH CH(OGOOH Asolution of 3,6,2OB-diacetyloxy-12,3-acetylamino-5apregnane (200 mg.) ina mixture of 5% sodium bicarbonate (2 ml.), methanol (6 ml.) and Water(2 ml.) is refluxed for 10 minutes in nitrogen stream. To the reactionmixture, there is added a large amount of Water whereby white crystalsare precipitated. The crystals are collected by filtration, Washed withWater, dried and chromatographed on alumina. form is evaporated andcrystallized from ethyl acetate to give3fi-hydroxy-1Zfi-acetylamino-ZOfi-acetyloxy-Sa-pregname (175 mg.) ascrystals melting at 219 to 221 C. [051 +18i4 (chloroform-methano1=l:1).

IR: 1123; 3586, 3237, 1732, 1636, 1567, 1248 cm.

Anal. Calcd. for C H O N: C, 71.56; H, 9.35. Found: C, 71.65; H, 9.92.

EXAMPLE 12 CH3 CH CO-NH (511(0000113) CH CO O- The eluate with chloro- IBBJOB-diacetyloxy-lh acetylamino 50c pregnane is subjected to hydrolysisas in Example 11 to give Elli-hydroxy-12oc-acetylamino-20fi acetyloxy 50c pregnane as crystals melting at 323 to 325 C. (decomp.) (crystallizedfrom a mixture of chloroform and methanol). a-b +l42i3(chloroform-methanol=1:1).

IR: 11232 3342, 1731, 1640, 1528, 1239 cm.-

Anal; Calcd. for C H O N: C, 71.56; H, 9.85; N,

3.34. Found: C, 71.47; H, 9.99; N, 3.13.

EXAMPLE 13 Preparation of 35,20fi-dihydroxy-12e-ac'etyIaminO-Sw pregnaneA mixture of 3,6,20/3-diacety1oxy-1Za-acetylaminO-Sapregnane mg.) andpotassium hydroxide (500 mg.) in methanol (10 ml.) is refluxed for 3hours in nitrogen stream. The reaction mixture is combined with waterand shaken with chloroform. The chloroform extract is dried and thesolvent removed. The residue is crystallized from hydrous methanol togive 3,8,20,8-dihydroxy- 12m-acetylaminQ-Suregnane (50 mg.) as crystalsmelting at 250 to 252 C.

EXAMPLE 14 Preparation of 3fi,20fl-dihydroxy 1.2}8 acetylamino 5apregnane and 3fi-acetyloxy-lZfi-acetylamino 20f? hydroxy-S wpregrzane rN Ha CH(OH) HO- CHsCOO- IR: P2 1 3 3219, 3070, 1738, 1645, 1580, 12-16cm.

Anal. Calcd. for C H O N: C, 71.56; H, 9.85; N, 3.34. Found: C, 71.75;H, 9.56; N, 3.32.

EXAMPLE Preparation of3/3-acetyZoxy-ZZa-acetylamin0-20/3-hydroay-Sa-pregnane omoo-nn mom Amixture of 35,20fi-dihydroxy-1Za-acetylamino-Sapregnane (97 mg.), aceticanhydride (1 ml.) and chloroform (2 ml.) is refluxed for 1 hour in anoil bath (temperature, 150 (3.). The reaction mixture is combined withwater and shaken with chloroform. The chloroform extract is Washed withwater, dried and the solvent evaporated. The residue is chromatographedon alumina. The eluate with benzene is evaporated and crystallized fromethyl acetate to give 3fl-acetyloxy-lZa-acetylaminO-2OB-hydroxy-5a-pregnane (73 mg.) as crystals melting at 221 to 223 C. [M+15: -2 (chloroform).

IR: 733 3 3374, 3270, 1734, 1623, 1557, 1248 cm.-

Anal. Calcd. for CH41O4N: c, 71.56; H, 9.85; N,

3.34. Found: C, 71.25; H, 9.86; N, 3.65.

1 4 EXAMPLE 16 Preparation of various acetyl derivatives of35,20B-dihydroxy-IZu-amino-Su-pregnane and 313,2011-dihydr0xy-IZB-rzmino-Su-pregnane A mixture (1.0 g.) of3,8,20,6-dihydroxy-1211-amino- Sa-pregnane and3,8,20fl-dihydroxy-12fl-amino Jet-pregname is dissolved in pyridine (15ml.) and acetic anhydride (7.5 ml.) and the resultant mixture is allowedto stand at room temperature (15 to 30 C.) one overnight. The reactionmixture is combined with water and shaken with ether. The ether extractis washed with water, 5% hydrochl-oric acid, 5% sodium carbonate andWater in order, dried and the solvent evaporated under reduced pressure.

The residue (1.2 g.) is chromatographed on neutral alumina (33 g.). Theeluate with benzene-benzene-chloroform (9: 1) is evaporated andcrystallized from ethyl acetate to give35-acetyloxy-12m-acetylamino-20B-hydroxy- Sa-pregnane (74 mg.) ascrystals melting at 220.5 to 222.5 C. The eluates withbenzene-chloroform (7:3)- chloroform are evaporated and crystallizedfrom ethyl acetate to give 3,8-acetyloxy-12fi acetylamino 20BhydroXy-Sa-pregnanc (288 mg.) as crystals melting at 200 to 202 C. Theeluates with petroleum ether-benzenebenzene obtained at the primarystage of the above chromatography are again chromatographed on alumina.The cluates with petroleum ether-benzene (1:2)-benzene are evaporatedand crystallized from ethyl acetate to give 3/3,203-diacetyloxy-l2a-acetylamino-5a-pregnane (180 mg.) as crystals meltingat 212 to 2l4.5 C. The eluate with chloroform is evaporated andcrystallized from a mixture of ethyl acetate and ether to give 313,205-diacetyloxy-12e-acetylamino-5a-pregnane mg.) as crystals melting at 211to 212 C. The uncrystallized portions on the above chromatographies arecombined and hydrolyzed by heating with 3 methanolic potassium hydroxidein nitrogen stream for 1 hour while refluxing. The reaction mixture iscondensed under reduced pressure, combined with water and shaken withchloroform. The chloroform extract is washed with water and evaporatedunder reduced pressure to dryness. The residue is crystallized frommethanol to give 35,205-dihydroxy- 12B-acetyIaminO-Sa-pregnane (153 mg.)as crystals melting at 297 to 298 C. (decomp.). The mother liquor isevaporated and crystallized from methanol to give 35-hydroxy-20/3-acetyloxy-12a-acetyIaminO-Suregnane (20 mg.) as crystalsmelting at 320 to 324 C. (decomp.).

What is claimed is:

1. A compound selected from the group consisting of the compounds of theformulae:

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF THE COMPOUNDS OF THEFORMULAE: